Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

Article Types

Countries / Regions

remove_circle_outline
remove_circle_outline
remove_circle_outline

Search Results (210)

Search Parameters:
Keywords = RFS—relapsed free survival

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
21 pages, 2099 KB  
Article
A Neuro-Immune Score Defines a Stromal–Neural and Immune-Segregated Microenvironment Associated with Poor Prognosis in Colorectal Cancer
by Hui Hu, Xu Yuan, Fang Peng, Na Shen and Yanjun Lu
Int. J. Mol. Sci. 2026, 27(16), 7231; https://doi.org/10.3390/ijms27167231 - 13 Aug 2026
Viewed by 208
Abstract
Colorectal cancer progression and therapeutic response are determined not only by tumor-intrinsic programs but also by neural, stromal, and immune components of the tumor microenvironment. However, biologically interpretable transcriptomic scores that jointly capture neural/stromal remodeling and immune activation remain limited. We developed a [...] Read more.
Colorectal cancer progression and therapeutic response are determined not only by tumor-intrinsic programs but also by neural, stromal, and immune components of the tumor microenvironment. However, biologically interpretable transcriptomic scores that jointly capture neural/stromal remodeling and immune activation remain limited. We developed a neuro-immune score (NIS), defined as the neural/stromal module score minus the immune activation module score. NIS was constructed using the combined TCGA-COAD/READ colorectal cancer cohort and externally evaluated in independent Gene Expression Omnibus (GEO) datasets. Single-cell RNA sequencing, focused ligand–receptor analysis, and spatial transcriptomics were further integrated to characterize the cellular origins, spatial organization, and potential mechanisms underlying NIS-associated biology. A high NIS (NIS-high) was associated with adverse prognosis in bulk transcriptomic cohorts. External validation demonstrated that a high NIS was significantly associated with worse disease-free survival/relapse-free survival (DFS/RFS) in GSE39582 and worse overall survival in GSE17536. A multi-cohort meta-analysis further supported a consistent association between NIS-high and poor clinical outcomes. Single-cell analysis localized the NIS-high signal mainly to glial-like cells, fibroblasts, pericytes, endothelial cells, and malignant epithelial cells, whereas CD8+ T cells and natural killer cells exhibited low NIS. Focused ligand–receptor analysis suggested that NIS-high cellular compartments may communicate with immune and tumor compartments through MIF-CD74/CXCR4, SPP1-CD44, extracellular matrix (ECM)–integrin, TGF-β, and immune checkpoint-related axes. Spatial transcriptomics further demonstrated that NIS-high regions were enriched in stromal, neural/glial-like, vascular/pericyte, and tumor–stromal niches, whereas NIS-low regions were associated with immune-activated and cytotoxic T/NK cell-rich areas. NIS captures a spatially organized state of the colorectal cancer microenvironment characterized by neural/stromal remodeling, activation of ECM and vascular/pericyte niches, and relatively reduced or spatially segregated immune activation. NIS may serve as a biologically interpretable microenvironment stratification score associated with adverse outcomes. It also provides a framework for future studies targeting stromal remodeling, myeloid-mediated immune regulation, neural-associated signaling, and antitumor immunity. Full article
(This article belongs to the Section Molecular Immunology)
Show Figures

Figure 1

19 pages, 2101 KB  
Article
Bidirectional Temporal Association Between Cytomegalovirus Reactivation and Graft-Versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Real-World Cohort Study
by Emel İşleyen, Simten Dağdaş, Bircan Kayaaslan, Funda Ceran, Mehmet Sezgin Pepeler, Ayşe Kaya, Gülten Korkmaz, Merve Ecem Erdoğan Yön, Fahir Öztürk, Ahmet Ceylan, Derya Kayardı and Gülsüm Özet
Viruses 2026, 18(8), 874; https://doi.org/10.3390/v18080874 - 11 Aug 2026
Viewed by 294
Abstract
Background: Cytomegalovirus (CMV) reactivation and graft-versus-host disease (GVHD) are major causes of morbidity and non-relapse mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although their association has been extensively investigated, the temporal relationship between these complications and their impact on survival remain incompletely [...] Read more.
Background: Cytomegalovirus (CMV) reactivation and graft-versus-host disease (GVHD) are major causes of morbidity and non-relapse mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although their association has been extensively investigated, the temporal relationship between these complications and their impact on survival remain incompletely understood, particularly in centers where routine letermovir prophylaxis is unavailable and CMV is managed using a pre-emptive treatment strategy. This study evaluated the bidirectional temporal association between CMV reactivation and GVHD using time-dependent analyses and assessed their impact on survival in a real-world allo-HSCT cohort. Methods: We retrospectively analyzed 100 consecutive adult patients who underwent allo-HSCT for hematologic malignancies between January 2016 and February 2025. CMV surveillance was performed by weekly quantitative CMV-DNA PCR, and reactivation was managed using a standardized pre-emptive treatment strategy. Patients who relapsed or died within the first 100 days after transplantation were excluded. The incidence, temporal sequence, risk factors, and prognostic impact of CMV reactivation and GVHD were evaluated. Overall survival (OS) and relapse-free survival (RFS) were estimated using the Kaplan–Meier method, while temporal associations were assessed using time-dependent Cox regression analyses. Results: CMV reactivation occurred in 72 patients (72%), whereas GVHD developed in 51 patients (51%). Among patients who experienced both complications, CMV reactivation preceded GVHD in 32 patients, while GVHD preceded CMV reactivation in 14 patients. Older recipient age (42.3 ± 13.5 vs. 35.4 ± 11.2 years, p = 0.018) and older donor age (37.2 ± 10.9 vs. 32.5 ± 9.7 years, p = 0.048) were associated with CMV reactivation. Older donor age was also associated with GVHD development (38.1 ± 10.7 vs. 33.6 ± 10.5 years, p = 0.037). The median time to CMV reactivation was 37 days, and CMV end-organ disease occurred in 13.9% of affected patients. No significant differences in OS or RFS were observed according to CMV reactivation or GVHD status in the day-100 landmark cohort. In the AML subgroup, both CMV reactivation and GVHD showed a trend toward inferior OS and RFS without reaching statistical significance. Time-dependent Cox regression demonstrated that CMV reactivation independently increased the subsequent risk of GVHD (HR 2.93, 95% CI 1.51–5.69; p = 0.001), whereas GVHD also independently increased the subsequent risk of CMV reactivation (HR 1.98, 95% CI 1.06–3.71; p = 0.032). Conclusions: CMV reactivation was highly prevalent after allo-HSCT and frequently preceded GVHD, supporting a bidirectional temporal relationship between these complications. Older donor age was associated with both CMV reactivation and GVHD. Although survival did not significantly differ according to CMV or GVHD status in this day-100 landmark cohort, clinically important CMV-related complications, including end-organ disease and platelet engraftment failure requiring eltrombopag, remained common. These findings indicate that a standardized pre-emptive strategy did not completely prevent CMV-associated morbidity. Because letermovir was not evaluated in this cohort, any potential benefit of prophylaxis should be interpreted as an inference from external evidence rather than as a direct finding of this study. Prospective multicenter studies incorporating immune reconstitution analyses are warranted. Full article
Show Figures

Figure 1

9 pages, 1590 KB  
Proceeding Paper
NDS: A Novel Deep Learning-Based Systems Biology Framework for Identifying Prognostic Biomarkers in Hepatocellular Carcinoma
by Muhammad Zurgham Akram and Mehwish Majeed
Med. Sci. Forum 2026, 48(1), 2; https://doi.org/10.3390/msf2026048002 - 31 Jul 2026
Viewed by 216
Abstract
Hepatocellular carcinoma (HCC) is an aggressive liver cancer requiring reliable biomarkers, while current approaches are limited by high-dimensional data and complex nonlinear gene interactions. In this study, differentially expressed genes were identified and fed to a deep autoencoder to reduce dimensionality, capture nonlinear [...] Read more.
Hepatocellular carcinoma (HCC) is an aggressive liver cancer requiring reliable biomarkers, while current approaches are limited by high-dimensional data and complex nonlinear gene interactions. In this study, differentially expressed genes were identified and fed to a deep autoencoder to reduce dimensionality, capture nonlinear interactions, and extract informative latent features. Predictive gene features were selected through mutual information (MI) ranking and LASSO regression and subsequently evaluated using logistic regression (LR), random forest (RF), and support vector machine (SVM) classifiers with 5-fold cross-validation (CV). The top 50 genes underwent enrichment analyses. Protein–protein interaction (PPI) networks were constructed to identify hub genes, followed by gene–drug interaction, transcription factor analysis, and survival validation. Enrichment analysis highlighted critical pathways involved in metabolic, signaling, and cell-cycle, and viral carcinogenesis. CV showed stable and high performance across classifiers (accuracy = 0.969, F1 ≈ 0.97), with RF and SVM achieving the highest AUC values (~0.983 and ~0.982). Independent tests showed excellent performance, with RF achieving perfect performance (1.0) across all evaluation metrics, confirming high feature discriminative power. Survival analysis showed that hub genes, including HSP90AB1, TUBA1B, PKM, H2AZ1, YWHAZ, ACLY, RAN, ILF2, KPNA2, and TXNRD1, were significantly associated with poor prognosis (HR > 1.5, p < 0.05), correlating with reduced overall, relapse-free, and disease-specific survival in HCC. The integrative novel framework effectively identifies biologically relevant biomarkers, providing insights into HCC mechanisms and potential targets for precision therapy. Full article
Show Figures

Figure 1

13 pages, 1501 KB  
Article
Long-Term Outcomes and Conditional Recurrence-Free Survival in Stage II Colon Cancer: The Impact of Surveillance and Recurrence Detection Strategies
by Mustafa Alperen Tunç, Ali Kaan Güren, Burak Paçacı, Fırat Akagündüz, Erkam Kocaaslan, Ahmet Demirel, Yeşim Ağyol, Pınar Erel, Nargiz Majidova, Nadiye Sever, Naz Tayyar Tunç, Nazım Can Demircan, Selver Işık, Abdussamed Çelebi, Ezgi Çoban, Osman Köstek, İbrahim Vedat Bayoğlu and Murat Sarı
J. Clin. Med. 2026, 15(13), 4901; https://doi.org/10.3390/jcm15134901 - 24 Jun 2026
Viewed by 390
Abstract
Background: Adjuvant therapy decisions for T3N0 stage II colon cancer remain controversial. This study evaluates long-term outcomes, recurrence patterns, and conditional relapse-free survival (RFS) in pathologic T3N0 colon cancer. Methods: This retrospective study included 306 patients undergoing curative resection for T3N0 colonic adenocarcinoma [...] Read more.
Background: Adjuvant therapy decisions for T3N0 stage II colon cancer remain controversial. This study evaluates long-term outcomes, recurrence patterns, and conditional relapse-free survival (RFS) in pathologic T3N0 colon cancer. Methods: This retrospective study included 306 patients undergoing curative resection for T3N0 colonic adenocarcinoma (1995–2020). Early recurrence was defined as recurrence or death within 3 years after surgery. Survival was estimated via Kaplan–Meier. Cox regression, adjusted for treatment eras, evaluated survival factors. Inverse Probability of Treatment Weighting (IPTW) minimized selection bias. Conditional RFS utilized a 5-year landmark analysis. Results: Over a 133-month median follow-up, 72 patients (23.5%) recurred. Most recurrences (81.9%) occurred within 3 years; only 9.7% after 5 years. Five- and 10-year OS rates were 80.9% and 70.4%. Inadequate lymph node dissection (<12 nodes) was performed in 29.7% of the entire cohort and was found to be an independent adverse prognostic factor for OS. Adjuvant chemotherapy lacked overall OS benefit, though IPTW analysis suggested potential benefit in patients with inadequate dissection. Conditional RFS (5–10 years) for patients recurrence-free at 60 months was 95.0%. Exploratory analyses showed descriptive differences in post-relapse survival based on the clinical triggers prompting radiological evaluation (marker-triggered versus symptom-triggered presentations). Conclusions: T3N0 colon cancer recurrences occur predominantly within the first 3–5 years after surgery. Inadequate lymph node dissection is the primary adverse prognostic factor. Although a 5-year follow-up period appears adequate for most patients, individualized extended surveillance may be considered for selected high-risk patients. Adjuvant treatment and follow-up strategies should be tailored according to surgical quality and risk factors. Full article
(This article belongs to the Section Oncology)
Show Figures

Figure 1

14 pages, 3688 KB  
Article
Parathyroid Hormone Modifies the Effect of Vitamin D Supplementation on Risk of Relapse or Death in Patients with Digestive Tract Cancer: A Post Hoc Subgroup Analysis of the AMATERASU Randomized Clinical Trial
by Akitaka Sasaki, Taisuke Akutsu, Hironori Ohdaira, Yutaka Suzuki, Ken Eto and Mitsuyoshi Urashima
Cancers 2026, 18(12), 2015; https://doi.org/10.3390/cancers18122015 - 22 Jun 2026
Viewed by 395
Abstract
Background/Objectives: Parathyroid hormone (PTH), which rises compensatory with vitamin D insufficiency and has been shown to down-regulate vitamin D receptor expression, represents a biologically plausible effect modifier. We investigated whether pretreatment serum PTH modifies the effect of postoperative vitamin D supplementation on [...] Read more.
Background/Objectives: Parathyroid hormone (PTH), which rises compensatory with vitamin D insufficiency and has been shown to down-regulate vitamin D receptor expression, represents a biologically plausible effect modifier. We investigated whether pretreatment serum PTH modifies the effect of postoperative vitamin D supplementation on relapse-free survival, and whether adding tumor p53 status further refines subgroup identification in an exploratory analysis. Methods: This post hoc analysis utilized data from the AMATERASU trial (UMIN000001977), a single-center, randomized, double-blind, placebo-controlled trial evaluating vitamin D3 (2000 IU/day) versus placebo in patients with curatively resected stage I–III digestive tract cancers (maximum follow-up, 7.5 years). Patients were dichotomized at the cohort median PTH (41 pg/mL). The primary outcome was relapse-free survival (RFS), analyzed using multivariable Cox proportional hazards models. Results: Of 417 randomized patients, 410 had baseline PTH data. In the lower PTH subgroup (≤41 pg/mL), vitamin D significantly improved RFS compared with placebo (fully adjusted hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.24–0.81; p = 0.008). Conversely, no benefit was observed in the higher PTH subgroup (>41 pg/mL; fully adjusted HR, 1.25; 95% CI, 0.64–2.44; p for interaction = 0.016). Exploratory stratification of 365 patients with p53 data showed that the supplementation benefit appeared greatest in patients with both low PTH (≤41 pg/mL) and p53-positive tumors (fully adjusted HR, 0.38; 95% CI, 0.18–0.78; p = 0.009). Conclusions: Pretreatment serum PTH is a candidate effect modifier of postoperative vitamin D supplementation in digestive tract cancers. Full article
Show Figures

Figure 1

11 pages, 732 KB  
Article
SFTPB Expression Predicts Favorable Survival in Lung Adenocarcinoma but Poor Prognosis in Lung Squamous Cell Carcinoma
by Soonsoo Kim, Hyowon Hong and Jae-Ho Lee
Medicina 2026, 62(6), 1140; https://doi.org/10.3390/medicina62061140 - 11 Jun 2026
Viewed by 719
Abstract
Background and Objectives: Surfactant protein B (SFTPB) is a surfactant-associated protein secreted by alveolar type II epithelial cells that plays a critical role in maintaining alveolar stability and surface tension. Although SFTPB is closely associated with pulmonary epithelial differentiation, its clinical significance [...] Read more.
Background and Objectives: Surfactant protein B (SFTPB) is a surfactant-associated protein secreted by alveolar type II epithelial cells that plays a critical role in maintaining alveolar stability and surface tension. Although SFTPB is closely associated with pulmonary epithelial differentiation, its clinical significance in different non-small cell lung cancer (NSCLC) subtypes remains unclear. This study investigated the clinicopathologic and prognostic significance of SFTPB expression in lung adenocarcinoma (AD) and lung squamous cell carcinoma (SCC) using The Cancer Genome Atlas (TCGA) dataset. Materials and Methods: SFTPB mRNA expression data and clinicopathologic information were obtained from TCGA cohorts of AD and SCC patients. Patients were stratified into high- and low-expression groups according to median SFTPB expression levels. Associations between SFTPB expression and clinicopathologic variables were analyzed, and correlation analyses were performed with major oncogenic genes. Overall survival (OS) and relapse-free survival (RFS) were evaluated using Kaplan–Meier survival analysis and log-rank testing. Multivariate Cox proportional hazards regression analyses were performed after adjustment for age, sex, and pathological stage. Results: In AD, high SFTPB expression was significantly associated with lower pathologic stage (p = 0.011) and lower N stage (p = 0.006). SFTPB expression showed significant negative correlations with EGFR (R = −0.140, p = 0.002) and BRAF (R = −0.177, p < 0.001) and a positive correlation with TP53 (R = 0.128, p = 0.004). Patients with high SFTPB expression demonstrated significantly improved OS compared with those with low expression (p < 0.001), while a trend toward prolonged RFS was observed without statistical significance (p = 0.089). Multivariate analysis confirmed high SFTPB expression as an independent favorable prognostic factor in AD (HR = 0.551, 95% CI = 0.405–0.748, p < 0.001). In SCC, high SFTPB expression was also significantly associated with lower pathologic stage (p = 0.009) and lower N stage (p = 0.007). SFTPB expression showed significant negative correlations with SOX2 (R = −0.176, p < 0.001), PIK3CA (R = −0.143, p = 0.002), and TP53 (R = −0.101, p = 0.026). In contrast to AD, high SFTPB expression was significantly associated with poorer OS (p = 0.026), whereas no significant difference in RFS was observed (p = 0.307). Multivariate analysis demonstrated that high SFTPB expression was an independent adverse prognostic factor in SCC (HR = 1.347, 95% CI = 1.028–1.767, p = 0.031). Conclusions: SFTPB expression is significantly associated with clinicopathologic characteristics and molecular signatures in both AD and SCC. However, its prognostic implications differ according to histologic subtype. High SFTPB expression independently predicts favorable survival in AD but unfavorable survival in SCC, suggesting distinct lineage-specific biological roles in NSCLC. These findings support SFTPB as a subtype-specific prognostic biomarker reflecting differential differentiation states and lineage context in NSCLC. Full article
Show Figures

Figure 1

19 pages, 1097 KB  
Review
The Prognostic Value of Circulating Tumor DNA for Clinical Outcomes in Patients Undergoing Hematopoietic Cell Transplantation: A Systematic Review and Meta-Analysis
by Do Tung Dac, Hirokazu Tanaka, Akiyoshi Takami and Jorge Luis Espinoza
Int. J. Mol. Sci. 2026, 27(11), 5076; https://doi.org/10.3390/ijms27115076 - 4 Jun 2026
Viewed by 711
Abstract
Relapse remains the leading cause of treatment failure following hematopoietic cell transplantation (HCT) for hematologic malignancies. Circulating tumor DNA (ctDNA) has emerged as a promising minimally invasive biomarker for measurable residual disease (MRD) assessment and early relapse detection; however, the prognostic significance of [...] Read more.
Relapse remains the leading cause of treatment failure following hematopoietic cell transplantation (HCT) for hematologic malignancies. Circulating tumor DNA (ctDNA) has emerged as a promising minimally invasive biomarker for measurable residual disease (MRD) assessment and early relapse detection; however, the prognostic significance of ctDNA in the post-transplant setting has not been comprehensively synthesized. We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines and registered the protocol in PROSPERO (CRD420261392100). PubMed, Embase, Web of Science, EBSCO, Cochrane CENTRAL, and supplementary sources were searched through November 2025. Eligible studies evaluated tumor-specific ctDNA or tumor-informed/tumor-associated cfDNA in patients undergoing allogeneic or autologous HCT for hematologic malignancies. Random-effects meta-analyses were performed for relapse/progression, overall survival (OS), and relapse-free/progression-free survival (RFS/PFS). Studies evaluating total cfDNA quantity, methylation-based cfDNA profiling, cfRNA, or chimerism-only monitoring were synthesized narratively. Ten observational cohort studies comprising 883 patients met inclusion criteria. Across acute leukemias, lymphomas, multiple myeloma, and myelodysplastic syndromes, ctDNA/cfDNA positivity was consistently associated with adverse outcomes. The pooled hazard ratio (HR) for relapse or disease progression was 12.57 (95% CI: 4.59–34.46; p < 0.001), while pooled HRs were 7.45 (95% CI: 4.11–13.48; p < 0.001) for OS and 4.46 (95% CI: 2.22–8.97; p < 0.001) for RFS/PFS. Although statistical heterogeneity was low, interpretation was limited by the relatively small number of studies contributing to each pooled endpoint. Narrative evidence additionally suggested that broader circulating nucleic acid approaches may provide complementary information regarding graft-versus-host disease, infection, and other post-transplant complications. Tumor-specific ctDNA positivity is consistently associated with increased relapse risk and inferior survival outcomes following HCT. These findings support further investigation of ctDNA-based MRD monitoring as a promising non-invasive biomarker for post-transplant molecular surveillance and risk stratification. However, prospective multicenter validation studies, assay standardization, and ctDNA-guided interventional trials remain necessary before routine clinical implementation can be recommended. Full article
Show Figures

Figure 1

14 pages, 825 KB  
Article
Analysis of Clinical Impact of CD33 rs12459419 Single-Nucleotide Polymorphism in AML Treated with Intensive Chemotherapy Without Gemtuzumab Ozogamicin
by Sophie Helfenstein, Inna Shaforostova, Katja Seipel, Marie-Noelle Kronig, Myriam Legros, Ulrike Bacher and Thomas Pabst
Int. J. Mol. Sci. 2026, 27(9), 4050; https://doi.org/10.3390/ijms27094050 - 30 Apr 2026
Viewed by 579
Abstract
The CD33 rs12459419 (C>T; Ala14Val) single-nucleotide polymorphism (SNP) has been reported to modulate treatment response and survival in pediatric patients with acute myeloid leukemia (AML) receiving gemtuzumab ozogamicin (GO), an anti-CD33 antibody linked to the cytotoxic compound calicheamicin. However, it remains unclear whether [...] Read more.
The CD33 rs12459419 (C>T; Ala14Val) single-nucleotide polymorphism (SNP) has been reported to modulate treatment response and survival in pediatric patients with acute myeloid leukemia (AML) receiving gemtuzumab ozogamicin (GO), an anti-CD33 antibody linked to the cytotoxic compound calicheamicin. However, it remains unclear whether this SNP also affects CD33 expression on leukemic blasts. Moreover, its prognostic significance in adult AML patients treated with standard chemotherapy without GO has not been investigated. In this study, we retrospectively genotyped 184 adult AML patients who received standard induction chemotherapy for the CD33 rs12459419 SNP genotype and collected CD33 expression data. The observed genotype distribution was 46% (n = 85) CC, 43% (n = 79) CT, and 11% (n = 20) TT. CD33 expression was detected in significantly higher proportions of leukemic blasts in patients with the CC genotype than those with the TT genotype (p = 0.0009). A similar trend was observed between the CT and TT genotypes (p = 0.06). No significant differences in clinical outcome were detected among the three genotype cohorts. Grouping CC and CT genotypes together based on their similar CD33 expression and comparing them to patients with the TT genotype also revealed no differences in overall survival (OS), event-free survival (EFS), or relapse-free survival (RFS). Using a proportion of 90% CD33-positive blasts to define high versus low expression groups also failed to identify a meaningful impact on OS, EFS, or RFS, either across genotypes or independent of genotype. In conclusion, our findings indicate that the CD33 rs12459419 SNP does not affect outcomes or survival in adult AML patients receiving standard chemotherapy in the absence of GO. Furthermore, no association was seen between CD33 expression and clinical outcomes between the three genotypes. To our knowledge, this is the first study to investigate the prognostic impact of the CD33 rs12459419 SNP per se on outcome and survival in adult AML patients treated with chemotherapy without GO. Validation in larger patient cohorts is required to conclusively rule out a prognostic role of the CD33 rs12459419 SNP in AML. Full article
(This article belongs to the Section Molecular Oncology)
Show Figures

Figure 1

12 pages, 1900 KB  
Article
Impact of Sarcopenia on Prognosis, Treatment Toxicity and Surgical Complications in Locally Advanced Gastric Cancer
by David da Silva Dias, Paulo Luz, Ana Fortuna, Ana Águas, Mafalda Machado, Beatriz Gosálbez, Rosa Farate, Rita Clemente Pinho, Ana Carmo Valente, José Leão Mendes, Marta Maria Seladas, Carolina Trabulo and Paula Ravasco
Cancers 2026, 18(9), 1430; https://doi.org/10.3390/cancers18091430 - 30 Apr 2026
Viewed by 850
Abstract
Background: Weight loss and skeletal muscle wasting are frequent in cancer and may influence treatment tolerance and outcomes. Computed tomography (CT) based body composition analysis at the third lumbar vertebra (L3) is an accurate method to quantify skeletal muscle in routine oncology care. [...] Read more.
Background: Weight loss and skeletal muscle wasting are frequent in cancer and may influence treatment tolerance and outcomes. Computed tomography (CT) based body composition analysis at the third lumbar vertebra (L3) is an accurate method to quantify skeletal muscle in routine oncology care. Methods: We performed a multicenter retrospective cohort study including 202 adults with locally advanced (stage IB–III) gastric cancer treated in four Portuguese hospitals (January 2020–December 2022). Skeletal muscle area (SMA) was assessed on baseline CT at the L3 vertebral level, using Data Analysis Facilitation Suite (DAFS) software v3.11.2, and skeletal muscle index (SMI) was subsequently calculated. Patients with low muscle quantity were classified as sarcopenic (below sex-specific SMI mean). We evaluated associations with relapse-free survival (RFS), overall survival (OS), FLOT chemotherapy dose-limiting toxicities (DLTs), and postoperative complications after gastrectomy. Results: Mean age was 69 years, 65% had ECOG PS 0, 53% received FLOT chemotherapy protocol. Mean SMI was 49.6 cm2/m2 in males and 40.9 cm2/m2 in females and correlated positively, though moderately, with BMI (p < 0.01; r = 0.424). Sarcopenia was not significantly associated with RFS (p = 0.186) or OS (p = 0.168) at 30-month follow-up. Although numerical differences were observed (64% vs. 56% of patients did not relapse and 74% vs. 63% were alive, for non-sarcopenic vs. sarcopenic patients). Sarcopenia was associated with a higher risk of DLTs (p = 0.021; OR 2.56, 95% CI 1.15–5.73) and postoperative complications (p = 0.024; OR 2.16, 95% CI 1.11–4.21). Conclusions: Sarcopenia significantly increases the risk of chemotherapy toxicity and postoperative complications in locally advanced gastric cancer. However, its effect on OS and RFS was not statistically significant at 30-month follow-up. Standardization of CT-based sarcopenia cut-offs remains a major barrier to clinical implementation. Full article
Show Figures

Figure 1

12 pages, 1315 KB  
Article
Feasibility of TP53-Mutated ctDNA Monitoring in High-Grade Endometrial Cancer Using Routine NGS
by Regine Marlin, Mehdi Jean-Laurent, Clarisse Joachim, Alexis Vallard, Sabrina Pennont, Valerie Suez-Panama, Mickaelle Rose, Sylviane Ulric-Gervaise, Sylvie Lusbec, Odile Bera, Aude Aline-Fardin and Coralie Ebring
Cancers 2026, 18(7), 1102; https://doi.org/10.3390/cancers18071102 - 28 Mar 2026
Cited by 1 | Viewed by 936
Abstract
Background/Objectives: High-grade endometrial cancer (EC) is associated with poor outcomes, particularly in populations with a high burden of aggressive histologies. There is a critical need for accessible biomarkers to improve prognostic assessment and guide clinical management. Methods: In this study, we evaluated the [...] Read more.
Background/Objectives: High-grade endometrial cancer (EC) is associated with poor outcomes, particularly in populations with a high burden of aggressive histologies. There is a critical need for accessible biomarkers to improve prognostic assessment and guide clinical management. Methods: In this study, we evaluated the feasibility and clinical relevance of monitoring circulating tumor DNA (ctDNA) by tracking somatic TP53 mutations using a routine next-generation sequencing (NGS) assay already implemented in diagnostic practice. Results: Among 21 patients with high-grade EC carrying TP53 mutations in the primary tumor, ctDNA was detectable in over 75% during follow-up. Baseline ctDNA detection strongly correlated with advanced disease: none of the FIGO I tumors were ctDNA-positive at diagnosis, whereas 73% of FIGO > I tumors showed detectable ctDNA. Patients with ctDNA detected at baseline had significantly poorer outcomes, with a 2-year recurrence-free survival (RFS) of 18% versus 60% and a 2-year overall survival (OS) of 40% versus 78%. Longitudinal monitoring revealed that postoperative persistence or reappearance of ctDNA was consistently associated with disease progression, often preceding radiological relapse. Conversely, early ctDNA clearance (at M4–M8) was associated with more favorable clinical trajectories. Conclusions: These findings highlight the potential role of ctDNA as a real-time molecular marker of minimal residual disease and tumor dynamics. Our results demonstrate that TP53-based ctDNA tracking using a standard NGS panel is feasible, sensitive, and clinically informative in high-grade EC. This approach may contribute to improving prognostic stratification and enabling more personalized, responsive clinical management, particularly in high-risk populations. Full article
(This article belongs to the Section Cancer Biomarkers)
Show Figures

Figure 1

16 pages, 557 KB  
Article
Inflammatory and Nutritional Indices as Prognostic Markers in Locally Advanced Gastric Cancer Treated with Neoadjuvant FLOT: A Retrospective Multicenter Study
by Süleyman Tuna Yolcu, Murat Günaltılı, Emine Ayaz Yolcu, Süleyman Sami Güzel, Nilay Şengül, Muhammed Mustafa Atcı, Kubilay Karaboyun, Gökmen Umut Erdem, Özkan Alan and Nebi Serkan Demirci
J. Clin. Med. 2026, 15(7), 2574; https://doi.org/10.3390/jcm15072574 - 27 Mar 2026
Cited by 1 | Viewed by 701
Abstract
Background/Objectives: Neoadjuvant chemotherapy is the standard of care for patients with locally advanced gastric cancer. Inflammatory and nutritional indices have been proposed as potential prognostic biomarkers in this setting. This study aimed to evaluate their association with pathological response and relapse-free survival [...] Read more.
Background/Objectives: Neoadjuvant chemotherapy is the standard of care for patients with locally advanced gastric cancer. Inflammatory and nutritional indices have been proposed as potential prognostic biomarkers in this setting. This study aimed to evaluate their association with pathological response and relapse-free survival (RFS) in patients with locally advanced gastric cancer treated with the perioperative FLOT regimen. Methods: This multicenter retrospective study included 120 patients treated with perioperative FLOT between 2018 and 2022. Pathological response was assessed using the Becker regression grading system. Pretreatment inflammatory and nutritional biomarkers were calculated from baseline data. Association with pathological responses and RFS were analyzed using logistic regression, Kaplan–Meier estimates, and Cox models. Results: Pathological response was strongly associated with higher radiologic and R0 resection rates and lower recurrence (all p < 0.001). None of the biomarkers correlated significantly with pathological response. Pathological response was the strongest prognostic factor for RFS (p < 0.001), while age (p = 0.011) and histologic subtype (p = 0.004) were also independent predictors. The CEA/albumin ratio showed a trend toward significance (HR 1.805; 95% CI 0.918–3.551; p = 0.087), and patients with lower ratios had longer RFS (median not reached vs. 15.8 months, p = 0.014). Conclusions: Pathological response remains the most powerful prognostic factor in locally advanced gastric cancer treated with perioperative FLOT. Although inflammatory and nutritional indices alone may not predict treatment response, the CEA/albumin ratio demonstrates potential prognostic value for RFS. Larger prospective studies with standardized cut-off values are warranted to validate these findings and to further explore the dynamic prognostic role of immunonutritional markers. Full article
(This article belongs to the Section Oncology)
Show Figures

Figure 1

15 pages, 2867 KB  
Article
Associations of Tumor Somatic Mutations and Genetic Alterations with Survival Outcomes in Melanoma Patients Treated with Ipilimumab
by Mohammad Ali Khaksar, Islam Eljilany, Ibrahim Yassine, Xiaoqing Yu, Jamie K. Teer, Jose R. Conejo-Garcia, Maureen Lyons, William LaFramboise and Ahmad A. Tarhini
J. Clin. Med. 2026, 15(6), 2355; https://doi.org/10.3390/jcm15062355 - 19 Mar 2026
Viewed by 1161
Abstract
Background: Identifying patients most likely to benefit from immune checkpoint inhibitors (ICIs) remains a significant challenge in advanced melanoma. We evaluated the association between tumor somatic mutations and clinical outcomes, focusing on relapse-free survival (RFS) and overall survival (OS) in locoregionally advanced melanoma [...] Read more.
Background: Identifying patients most likely to benefit from immune checkpoint inhibitors (ICIs) remains a significant challenge in advanced melanoma. We evaluated the association between tumor somatic mutations and clinical outcomes, focusing on relapse-free survival (RFS) and overall survival (OS) in locoregionally advanced melanoma patients treated with neoadjuvant ipilimumab. Methods: Tumor specimens and matched peripheral blood samples from 22 patients underwent whole-exome sequencing (WES) to identify non-synonymous somatic mutations. Tumor mutational burden (TMB) was quantified, and specific mutations were analyzed for associations with survival outcomes. Results: The analysis revealed a mutational landscape dominated by single-nucleotide missense mutations with a median TMB of 11.4 mutations/MB. BRAF and NRAS mutations were detected in 73% of patients and exhibited mutual exclusivity and concurrence patterns (p < 0.05). Positional clustering identified NRAS and SLC35B4 as key contributors to melanoma (FDR p-value < 0.05). Log-rank analysis indicated that mutations in ODZ1, USP34, CEP192, EML5, KIAA1797, ATAD5, and ANKHD1–EIF4EBP were associated with shorter survival outcomes (RFS or OS). The associations remained significant in both univariate and multivariable Cox regression models adjusted for TMB. These genes can be broadly grouped into functional categories relevant to tumor progression and immune modulation. In applying multiple testing correction, none maintained statistical significance, indicating that these findings should be interpreted as exploratory and require validation in independent cohorts. Conclusions: This study identified tumor genomic alterations associated with clinical outcomes in melanoma patients treated with neoadjuvant ipilimumab, suggesting their potential role in anti-tumor immunity. These findings warrant further investigation in larger cohorts and across other ICIs in melanoma and other malignancies. Full article
(This article belongs to the Section Oncology)
Show Figures

Figure 1

10 pages, 726 KB  
Article
The Outcomes of Myeloid Sarcoma in 64 Pediatric Patients and the Impact of Allogeneic Hematopoietic Stem Cell Transplantation on Treatment Results
by Magdalena Samborska, Jolanta Skalska-Sadowska, Jacek Wachowiak, Małgorzata Czogała, Walentyna Balwierz, Szymon Skoczeń, Natalia Bartoszewicz, Jan Styczyński, Tomasz Ociepa, Tomasz Urasiński, Grażyna Wróbel, Krzysztof Kałwak, Katarzyna Muszyńska-Rosłan, Anna Szmydki-Baran, Iwona Malinowska, Paweł Łaguna, Agnieszka Mizia-Malarz, Renata Tomaszewska, Tomasz Szczepański, Agnieszka Chodała-Grzywacz, Grażyna Karolczyk, Lucyna Maciejka-Kembłowska, Marta Kozłowska, Ninela Irga-Jaworska, Katarzyna Mycko, Wanda Badowska, Katarzyna Bobeff, Wojciech Młynarski, Radosław Chaber, Joanna Zawitkowska, Katarzyna Drabko and Katarzyna Derwichadd Show full author list remove Hide full author list
Children 2026, 13(3), 343; https://doi.org/10.3390/children13030343 - 27 Feb 2026
Cited by 1 | Viewed by 1305
Abstract
Background: Myeloid sarcoma (MS) is a malignant extramedullary tumor that occurs in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myeloid leukemia (CML). The standard first-line treatment for MS is intensive chemotherapy according to the AML protocol, regardless of bone [...] Read more.
Background: Myeloid sarcoma (MS) is a malignant extramedullary tumor that occurs in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myeloid leukemia (CML). The standard first-line treatment for MS is intensive chemotherapy according to the AML protocol, regardless of bone marrow involvement. The role of allogeneic hematopoietic stem cell transplantation (alloHSCT) in the treatment of pediatric patients with MS requires further investigation. The aim of the study was to evaluate treatment outcomes for MS in pediatric patients with a focus on assessing the impact of allogeneic hematopoietic stem cell transplantation (alloHSCT) on treatment efficacy. Material and Methods: The study included 64 patients aged 0 to 19 years from 15 pediatric oncology centers in Poland who were diagnosed with MS between 1998 and 2024. An Excel database was created to collect data on clinical features and treatment methods and outcomes. Results: The probability of 5-year overall survival (pOS) for the entire cohort was 0.63 ± 0.07, while the 5-year event-free survival (pEFS) and 5-year relapse-free survival (pRFS) were 0.62 ± 0.07 and 0.72 ± 0.07, respectively. Treatment outcomes were compared between patients who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) in first complete remission (ICR) (n1 = 17/64; 27%) and those who did not receive alloHSCT (n2 = 47/64; 73%). In the alloHSCT group (n1), the estimated survival probabilities were pOS = 0.49 ± 0.13, pEFS = 0.44 ± 0.14, and pRFS = 0.40 ± 0.14. In the non-alloHSCT group (n2), these values were pOS = 0.68 ± 0.08, pEFS = 0.68 ± 0.08, and pRFS = 0.84 ± 0.06. The difference in pRFS between groups n1 and n2 was statistically significant (p = 0.0049). Extramedullary relapses were more frequently observed in patients who had undergone allogeneic hematopoietic stem cell transplantation (alloHSCT) (p = 0.0001). Conclusions: Allogeneic hematopoietic stem cell transplantation (alloHSCT) does not improve the outcome of patients with MS. Further research is needed to identify effective strategies for sustaining remission in patients with MS after alloHSCT. Full article
(This article belongs to the Section Pediatric Hematology & Oncology)
Show Figures

Figure 1

10 pages, 621 KB  
Article
Baseline Red Blood Cell Distribution Width as a Prognostic Marker in High-Risk Resected Cutaneous Melanoma
by Omer Ekin and Oktay Halit Aktepe
J. Clin. Med. 2026, 15(5), 1757; https://doi.org/10.3390/jcm15051757 - 26 Feb 2026
Cited by 1 | Viewed by 515
Abstract
Background and Objectives: High-risk resected cutaneous melanoma carries a substantial risk of recurrence, and additional host-related prognostic biomarkers are needed beyond conventional tumor-centered factors. Red blood cell distribution width (RDW) reflects systemic inflammation and physiological stress and may provide incremental prognostic information. Materials [...] Read more.
Background and Objectives: High-risk resected cutaneous melanoma carries a substantial risk of recurrence, and additional host-related prognostic biomarkers are needed beyond conventional tumor-centered factors. Red blood cell distribution width (RDW) reflects systemic inflammation and physiological stress and may provide incremental prognostic information. Materials and Methods: In this retrospective cohort study, 164 patients with stage II–III cutaneous melanoma who underwent curative-intent surgical resection were analyzed. A receiver operating characteristic (ROC) curve analysis determined the optimal RDW cut-off for relapse-free survival (RFS), which was 14.2%. Patients were categorized into low and high RDW groups accordingly. Survival probabilities were estimated using the Kaplan–Meier method and compared with the log-rank test. Univariate and multivariate Cox proportional hazards regression models were used to evaluate associations between RDW status, clinicopathological variables, and RFS. Results: During a median follow-up of 58.3 months, patients with high RDW had significantly shorter RFS compared with those with low RDW. In univariate analysis, elevated RDW was associated with an increased risk of recurrence (HR 2.79, 95% CI 1.39–5.58; p = 0.004). After adjustment for key prognostic factors (e.g., stage, Breslow, age, adjuvant therapy), high RDW remained an independent predictor of inferior RFS (HR 2.74, 95% CI 1.37–5.47; p = 0.004). Stage III disease also independently predicted worse RFS (HR 4.67, 95% CI 2.04–10.68; p < 0.001). Conclusions: Baseline RDW independently predicts RFS in high-risk resected stage II–III cutaneous melanoma and may enhance prognostic stratification using a simple, widely available biomarker. Full article
(This article belongs to the Section Oncology)
Show Figures

Figure 1

12 pages, 1918 KB  
Article
18F-FDG PET/CT for Risk Stratification and Prognosis of Patients with Hypermetabolic Gastrointestinal Stromal Tumors
by Li Zhang, Yu Liu, Chunxia Qin, Huanyu Chen, Yujun Wu, Jinbo Gui, Jingwen Wang, Yong He, Xiaoli Lan and Wei Cao
Cancers 2026, 18(5), 717; https://doi.org/10.3390/cancers18050717 - 24 Feb 2026
Viewed by 787
Abstract
Objectives: We aimed to evaluate the value of various PET parameters derived from 18F- FDG PET/CT for risk stratification and prognosis of hypermetabolic gastrointestinal stromal tumors (GISTs). Methods: This study included 43 patients who underwent 18F-FDG PET/CT imaging with hypermetabolic (SUVmax [...] Read more.
Objectives: We aimed to evaluate the value of various PET parameters derived from 18F- FDG PET/CT for risk stratification and prognosis of hypermetabolic gastrointestinal stromal tumors (GISTs). Methods: This study included 43 patients who underwent 18F-FDG PET/CT imaging with hypermetabolic (SUVmax > 2.5) GIST and underwent surgical treatment. Clinicopathological characteristics, risk stratification, PET parameters including standard uptake values (SUVs), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and heterogeneity index (HI), and follow-up data were reviewed. The relationship between PET parameters and risk stratification based on the modified National Institutes of Health (NIH) criteria was analyzed. PET parameters were assessed to predict relapse-free survival (RFS) and overall survival (OS), based on Cox regression analysis and Kaplan–Meier analysis. Results: The median follow-up duration was 50 months. During follow-up, 11 patients (25.58%) experienced recurrence and 8 (18.60%) died. In risk stratification, the high-risk group exhibited more frequent extragastric location, larger tumor size, higher mitotic count, and elevated PET parameters except SUVmax. MTV (≤32.68 vs. >32.68, 95% CI: 1.358–72.048, p = 0.024) emerged as an independent PET parameter of risk stratification. In univariate analysis, tumor location (gastric vs. extragastric), SUVmax (≤10.25 vs. >10.25), and HI (≤2.44 vs. >2.44) were significant prognostic factors for RFS. Tumor location and SUVmax were significant to OS on univariate analysis. However, in multivariate analysis, only SUVmax (95% CI: 1.549–46.071, p = 0.014) was an independent prognostic factor for both RFS and OS. Conclusions: 18F-FDG PET/CT demonstrates predictive value for hypermetabolic GIST patients. MTV derived from 18F-FDG PET/CT improves the ability of predicting risk stratification. SUVmax is an effective predictor of both RFS and OS. Full article
(This article belongs to the Special Issue Advances in Medical Imaging for Cancer Detection and Diagnosis)
Show Figures

Figure 1

Back to TopTop